Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells

  • Nur Izzati Mansor Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Medical Genetics Unit, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia https://orcid.org/0000-0002-3650-1494
  • Carolindah Makena Ntimi Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Medical Genetics Unit, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia https://orcid.org/0000-0001-6916-313X
  • Noraishah Mydin Abdul-Aziz Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • King-Hwa Ling Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Medical Genetics Unit, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia https://orcid.org/0000-0002-3968-7263
  • Aishah Adam Pharmacology and Toxicology Research Laboratory, Faculty of Pharmacy, Puncak Alam Campus, Universiti Teknologi MARA, Shah Alam, Selangor, Malaysia
  • Rozita Rosli Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Medical Genetics Unit, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia https://orcid.org/0000-0001-6381-9935
  • Zurina Hassan Centre for Drug Research, Universiti Sains Malaysia, Gelugor, Penang, Malaysia https://orcid.org/0000-0003-3205-4612
  • Norshariza Nordin Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Medical Genetics Unit, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia https://orcid.org/0000-0003-1019-0496
Keywords: Amyloid β-peptides, Alzheimer’s disease, reactive oxygen species, oxidative stress, 46C mouse embryonic stem cell

Abstract

One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer’s disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Ab peptides (Aβ1-42 and Aβ25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies (EBs) in the absence of leukemia inhibitory factor (LIF), followed by the addition of all-trans retinoic acid (ATRA) as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular ROS production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.

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Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells
Published
2020-03-06
How to Cite
1.
Mansor NI, Ntimi CM, Abdul-Aziz NM, Ling K-H, Adam A, Rosli R, Hassan Z, Nordin N. Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells. Bosn J of Basic Med Sci [Internet]. 2020Mar.6 [cited 2020Apr.8];. Available from: http://bjbms.org/ojs/index.php/bjbms/article/view/4639
Section
Short Communication